Over the years various attempts have been made to devise effective process technology for producing p-bromotoluene in good yield and of high purity. This has proven to be a difficult task, as most processes tend to produce mixtures of o-bromotoluene along with p-bromotoluene. Because of their close boiling points the separation of these isomers from each other in a large scale plant installation requires a distillation column of very high efficiency.
The magnitude of the problem and the extensive efforts that have been devoted toward producing either o-bromotoluene or p-bromotoluene in high yield and purity is illustrated by the following sampling of published accounts of research in the field:
U.S. Pat. No. 3,303,224 (1967) describes use of BaBrO.sub.3 with one equivalent of H.sub.2 SO.sub.4 and oxalic acid to brominate toluene in an aqueous medium, followed by extraction with methylene chloride. An 85% yield of a bromotoluene fraction was obtained. Infrared analysis indicated the product to be 66% ortho-, 33% p- and 1% m-bromotoluene.
Japan Kokai 52-042825 (1977) describes refluxing a 51:49 para-ortho) mixture of bromotoluenes with beta-cyclodextrin in 75% aqueous acetic acid followed by extracting the precipitate with hot diethyl ether to obtain 99.5-0.5 ortho-para. The liquid phase from which the precipitate had been removed gave a mixture of 28% o-bromotoluene and 72% p-bromotoluene.
Japan Kokai 57-077631 (1982) refers, inter alia, to vapor phase bromination of toluene using as catalysts, zeolites with average pore diameters of 5 to 13 Angstroms.
Organometallics, 1986, 5(1), 168-173 refers, inter alia, to bromination of tolyl(octaethylporphinato)rhodium to produce bromotoluene with high regioselectivity.
J. Chem. Soc., Chem. Commun., 1987, 10, 752-3; J Org. Chem., 1988, 53(23), 5545-7; and Israel 79627 A1 (1992) refer, inter alia, to formation of p-bromotoluene by use of BrF as the brominating agent.
J. Org. Chem. 1988, 53(9), 2093-4 refers to use of CuBr.sub.2 adsorbed onto alumina as a selective brominating agent. Synthesis of p-bromotoluene is referred to.
Zeolites, 1987,7(6), 499-502 describes ring bromination of alkylbenzenes, including toluene, using zeolite 13X or mordenite after introduction of Fe (III) ions.
J. Chem. Soc., Chem. Commun., 1989, 10, 653-4 indicates that propylene oxide, acting as an HBr scavenger, greatly improved the selectivity of zeolite-catalyzed bromination of toluene to form almost pure p-bromotoluene.
Zeolites, 1991, 11(6), 617-21 describes results from a study of the liquid phase bromination of aromatics, including toluene, catalyzed by zeolites. An explanation is given for the low selectivities obtained even though zeolite catalysts are used.
Synth. Commun., 1992, 22(8), 1095-9 describes formation of 65:35 mixtures of ring-brominated derivatives of toluene using molecular bromine adsorbed on the surface of alumina, and no solvent. A 90% yield was achieved.
Synth. Commun., 1992, 22(17), 2513-20 refers to preparation of p-bromotoluene from bromination of toluene with bromosaccharin in pyridinium poly(hydrogen fluoride).
J. Chem. Soc. Pak., 1992, 14(3), 212-14 reports formation of p-bromotoluene in 70% yield by use of a mixture of KBr and NaNO.sub.3 in sulfuric acid (60% vol./vol.).
Ind. Chem. Libr., 1995, 7, 17-28 refers to use of cupric bromide supported on alumina to brominate, inter alia, toluene.
Ind. Chem. Libr., 1995, 7, 49-64 indicates that toluene can be brominated in quantitative yield and with excellent para-selectivity by use of tert-butyl hypobromite in the presence of proton-exchanged zeolite X.
Chem. Commun. (Cambridge), 1996, 4, 467-8 indicates that toluene can be brominated with bromine and a stoichiometric amount of zeolite NaY in high yield and with high selectivity to p-bromotoluene, and that the zeolite is easily regenerated by heating.
p-Bromotoluene is an important intermediate for the commercial synthesis of bioactive compounds by at least two large industrial concerns. Although some of the foregoing methods are effective for producing p-bromotoluene in high yields and good selectivities in laboratory-scale operations, the need exists for an efficient process which can provide high purity p-bromotoluene in good yields on an industrial scale and within the limits of economic constraints. It is believed that this invention makes possible the achievement of these objectives.